Neurofibromatosis type 1-associated brain tumors

Abstract

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder that predisposes patients to develop benign and malignant neoplasms, most often due to a loss of function mutation in the neurofibromatosis type 1 (NF1) gene. Neurofibromin, the protein product of NF1, regulates the inactivation of the Ras pathway, and thus acts as a tumor suppressor. Located in neurons, Schwann cells, and melanocytes, a decrease in neurofibromin predisposes patients with NF1 to tumors in both the central and peripheral nervous systems. Interestingly, brain tumors associated with NF1 often follow a more benign course than their sporadic counterparts and are often found in different locations. Thus, these tumors are often observed without tumor-directed therapy, unless clinical progression is noted, and then they are treated with surgery, chemotherapy or radiation. Current treatment trials seek to create more targeted therapies for specific tumor types associated with NF1 in order to increase efficacy and decrease treatment-related morbidity. This review will examine the most common types of brain tumors associated with NF1, including pilocytic astrocytomas, optic pathway gliomas, brainstem gliomas and glioblastomas, and will provide an overview of the clinical implications, current treatments, and ongoing clinical trials for these tumors.